A quantitative formulation of the functional circuitry of the dorsal column nuclei, embodied as a working computer model, is the central goal of this project. This goal requires definition of major cell types within the nuclei and their inputs, output and interactions. Quantitative measures of response parameters as a function of variations in input parameters are also necessary. The major outlines of the basic circuitry for the nuclei have been developed from earlier work in this laboratory using population analysis of single cell data and characterization of inhibitory processes. We have also obtained input- output transforms relating output from the nuclei and inhibition within the nuclei to frequency and amplitude parameters of several major inputs. In the coming grant period further definition of the basic model and of input-output transforms will be obtained by examining single output elements. Introduction of pharmacological agents known to interact with inhibition in the nuclei, will be tested for their ability to differentially influence defined circuit elements. Theoretical calculations related to formulation of a working computer model will be further explored.